Experiments are proposed to investigate hypothalamic control of the onset of puberty in female rhesus monkeys and guinea pigs from the viewpoint of comparative neuroendocrinology. First, tests will be made to determine whether the hypotheses of "differential sensitivity to ovarian steroid" or "establishment of positive feedback system" at level of the hypothalamus is the key factor for the onset of puberty. Specifically, PMSG will be administered at different prepubertal ages in an attempt to induce precocious puberty as defined by a cyclic series of ovulations, and the minimum age of its effectiveness will be examined to determine hypothalamus maturation. The precocious development of the positive feedback response to estrogen will also be evaluated in other immature animals wherein the possible negative feedback effects of ovarian secretions have been removed by ovariectomy. Hormone measurements (LH, FSH, estrogen and progesterone) by radioimmunoassay and ovarian visualization by laparoscopy or laparotomy will confirm these events. Secondly, direct evidence of hypothalamic involvement in the onset of puberty will be examined by lesion or stimulation methods. Clinical observations in the human subject suggest that the major lesion site for precocious sexual maturation is located in the posterior part of the hypothalamus, while experimental observations in the rat identify the anterior part of the hypothalamus to be the most affected area. Radiofrequency lesions will be placed in various parts of the hypothalamus to induce precocious puberty as defined above. Furthermore, various hypothalamic sites will be stimulated electrically to identify those sites which may be involved in release of gonadotropin. Results from these projects will not only fill a gap in neuroendocrinology, to reconcile the problem of species difference, but will also clarify the essential role of the hypothalamus controlling the onset of puberty.